{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:52:50Z","timestamp":1777503170570,"version":"3.51.4"},"reference-count":64,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Qihang Special Program of Enshi Prefecture","award":["No. D20220022"],"award-info":[{"award-number":["No. D20220022"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cancer Inform"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To elucidate mechanistic links among selenium measures, selenium-related genes, and immune traits in laryngeal carcinoma (LC) by integrating Mendelian randomization, bulk transcriptomic, and single-cell analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Two-sample Mendelian randomization (MR) was used to evaluate the causal effects of selenium measures and genetically predicted expression of selenium-related genes instrumented by eQTLs on LC risk, and immune traits were screened as candidate mediators via a directionality-based filter. We then examined PNPO expression in relation to pathway activity and immune infiltration in the TCGA and GEO cohorts. Single-cell RNA sequencing was further analyzed to characterize PNPO-associated programs in malignant epithelial and immune cells. The scPagwas and deconvolution algorithms were applied to prioritize disease-relevant T-cell subsets, and hdWGCNA was used to identify phenotype-associated gene modules. Intercellular communication, signaling activity, developmental trajectories, and transcription factor programs were evaluated in complementary analyses. The reporting of this study conforms to the STROBE-MR guideline for Mendelian randomization studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Genetically predicted selenium measures showed no evidence of a causal association with LC risk. In contrast, PNPO showed evidence consistent with involvement in LC susceptibility, potentially involving CD127\n                      <jats:sup>\u2212<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells. In bulk transcriptomic cohorts, tumors with low PNPO expression were enriched for oncogenic pathways and were associated with poorer survival. PNPO expression correlated positively with inferred CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell infiltration. At single-cell resolution, PNPO\n                      <jats:sup>\u2212<\/jats:sup>\n                      malignant epithelial cells displayed transcriptional features consistent with stemness, drug resistance, and immune-evasion programs. We further identified a pre-exhausted CD127\n                      <jats:sup>\u2212<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell subset with distinct molecular and functional characteristics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      These analyses implicate PNPO-linked vitamin B6 metabolism and a pre-exhausted CD127\n                      <jats:sup>\u2212<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell state in LC, highlighting candidates for mechanistic validation and potential therapeutic exploration.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/11769351261438477","type":"journal-article","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T12:33:17Z","timestamp":1776515597000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integration of Multi-Omics Data Identifies the Role of the Selenium-Related Gene PNPO and Pre-exhausted CD127\n                    <sup>\u2212<\/sup>\n                    CD8\n                    <sup>+<\/sup>\n                    T Cells in Laryngeal Carcinoma"],"prefix":"10.1177","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1482-730X","authenticated-orcid":false,"given":"Lin","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Affiliated Minda Hospital of Hubei Minzu University, Enshi, Hubei, China"},{"name":"Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Disease, Affiliated Minda Hospital of Hubei Minzu University, Enshi, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7073-059X","authenticated-orcid":false,"given":"Lin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Plastic and Aesthetic Surgery, Affiliated Minda Hospital of Hubei Minzu University, Enshi, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6384-1411","authenticated-orcid":false,"given":"Cheng","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Plastic and Aesthetic Surgery, Affiliated Minda Hospital of Hubei Minzu University, Enshi, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0528-6177","authenticated-orcid":false,"given":"Yao","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Affiliated Minda Hospital of Hubei Minzu University, Enshi, Hubei, China"},{"name":"Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Disease, Affiliated Minda Hospital of Hubei Minzu University, Enshi, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,4,18]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.17849\/insm-51-2-92-110.1"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.07.011"},{"issue":"1","key":"e_1_3_3_4_2","first-page":"1","article-title":"Factors influencing tumour relapse after total laryngectomy","volume":"1","author":"Nikolaou A","year":"2005","unstructured":"Nikolaou A, Markou K, Petridis D, Vlachtsis K, Nalbantian M, Daniilidis L. 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